Automatic activation of medical processes

ABSTRACT

Systems and methods involve automatic activation, de-activation or modification of therapies or other medical processes based on brain state. A medical system includes a sensor system having one or more sensors configured to sense signals related to the brain state of the patient. A brain state analyzer detects various brain states, including sleep stage and/or brain seizures. A controller uses the brain state detection information to control a medical system configured to perform at least one respiratory or cardiac process. Methods involve sensing signals related to brain state and determining the brain state of a patient based on the sensed signals. At least one respiratory or cardiac medical process is controlled based on the patient&#39;s brain state.

RELATED PATENT DOCUMENTS

This application claims the benefit of Provisional Patent ApplicationSer. No. 60/504,381, filed on Sep. 18, 2003, to which priority isclaimed pursuant to 35 U.S.C. §119(e) and which is hereby incorporatedherein by reference in its entirety.

FIELD OF THE INVENTION

The invention relates generally to implantable medical monitoring and/orstimulation systems and methods, and more particularly to monitoringand/or stimulation systems and methods that activate therapy based onbrain activity.

BACKGROUND OF THE INVENTION

Disordered breathing refers to a wide spectrum of respiratory conditionsthat involve disruption of the normal respiratory cycle. Althoughdisordered breathing typically occurs during sleep, the condition mayalso occur while the patient is awake. Unfortunately, disorderedbreathing is often undiagnosed. If left untreated, the effects ofdisordered breathing may result in serious health consequences for thepatient.

Various types of disordered respiration have been identified, including,for example, apnea, hypopnea, dyspnea, hyperpnea, tachypnea, andperiodic breathing, including Cheyne-Stokes respiration (CSR). Apnea isa fairly common disorder characterized by periods of interruptedbreathing. Apnea is typically classified based on its etiology. One typeof apnea, denoted obstructive apnea, occurs when the patient's airway isobstructed by the collapse of soft tissue in the rear of the throat.Central apnea is caused by a derangement of the central nervous systemcontrol of respiration. The patient ceases to breathe when controlsignals from the brain to the respiratory muscles are absent orinterrupted. Mixed apnea is a combination of the central and obstructiveapnea types. Regardless of the type of apnea, people experiencing anapnea event stop breathing for a period of time. The cessation ofbreathing may occur repeatedly during sleep, sometimes hundreds of timesa night and sometimes for a minute or longer.

Periodic breathing is characterized by cyclic respiratory patterns thatmay exhibit rhythmic rises and falls in tidal volume. Cheyne-Stokesrespiration is a specific form of periodic breathing wherein the tidalvolume decreases to zero resulting in apneic intervals. The breathinginterruptions of periodic breathing and CSR may be associated withcentral apnea, or may be obstructive in nature. CSR is frequentlyobserved in patients with congestive heart failure (CHF) and isassociated with an increased risk of accelerated CHF progression.Because of the cardiovascular implications, therapy forrespiration-related sleep disorders is of particular interest.

Disordered breathing affects a significant percentage of people. Sleepdisordered breathing is particularly prevalent and is associated withexcessive daytime sleepiness, systemic hypertension, increased risk ofstroke, angina and myocardial infarction. Respiratory disruption may beparticularly serious for patients concurrently suffering fromcardiovascular deficiencies, such as congestive heart failure.

SUMMARY OF THE INVENTION

Embodiments of the invention involve automatic control of therapies orother medical processes based on brain activity. Automatic control mayinvolve automatic activation, de-activation and/or modification of suchtherapies and processes. In accordance with an embodiment of theinvention, a system includes a sensor system having one or more sensorsconfigured to sense signals related to the brain activity of thepatient. A brain activity analyzer detects various brain states,including, for example, sleep state/stage and/or brain seizures. Thebrain activity detector may also be configured to discriminate betweensleep and wakefulness. A controller uses the brain state detectioninformation to control a medical system configured to perform at leastone respiratory or cardiac process.

Other embodiments of the invention include at least one of an EEG sensorand an EMG sensor configured for one or more of detecting brain state.One or more sensors may be positioned on a respiratory mask of arespiratory device, such as a positive airway pressure therapy device.Further embodiments include a cardiac rhythm management device, whereinthe cardiac process may involve one or both of a cardiac therapy processand a breathing therapy process. The cardiac process may further involvea diagnostic process and/or a monitoring process.

In accordance with another embodiment of the invention, a methodinvolves sensing signals related to brain state and determining thebrain state of a patient based on the sensed signals. At least onerespiratory or cardiac medical process is activated, de-activated,modified or otherwise controlled based on the patient's brain state.

Further embodiments of methods in accordance with the invention involvesensing the signals related to brain state using EEG signals and/or EMGsignals. Sensing signals related to brain state may further involvesensing signals related to sleep stage. Sensing signals related to brainstate may involve sensing seizure, and activating the medical processmay involve activating, de-activating, modifying or otherwisecontrolling arrhythmia therapy based on seizure detection.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a flow chart illustrating a method of controlling a medicalprocess using brain state information in accordance with embodiments ofthe invention;

FIGS. 1B-1D are block diagrams of systems implementing control ofmedical processes using brain activity information in accordance withembodiments of the invention;

FIG. 1E illustrates graphs of signals from an EEG sensor and an EMGsensor useful for determining brain state in accordance with embodimentsof the invention;

FIGS. 1F-1H and 1J are diagrams illustrating various configurations ofsensors coupled to an implanted medical device that uses brain stateinformation to activate, de-activate, and/or modify therapy inaccordance with embodiments of the invention;

FIG. 2 is a flow chart illustrating a brain state algorithm based onsignals from an EEG sensor in accordance with embodiments of theinvention;

FIG. 3 is a graph of a normal respiration signal measured by atransthoracic impedance sensor that may be utilized for monitoring,diagnosis and/or therapy in accordance with embodiments of theinvention;

FIG. 4 is a respiration signal graph illustrating respiration intervalsused for disordered breathing detection according to embodiments of theinvention;

FIG. 5 is a graph of a respiration signal illustrating various intervalsthat may be used for detection of apnea in accordance with embodimentsof the invention;

FIG. 6 is a respiration graph illustrating abnormally shallowrespiration utilized in detection of disordered breathing in accordancewith embodiments of the invention;

FIG. 7 is a flow chart illustrating a method of apnea and/or hypopneadetection according to embodiments of the invention;

FIG. 8 illustrates a medical system including an implantable cardiacrhythm management device that cooperates with a patient-externalrespiration therapy device to provide coordinated patient monitoring,diagnosis and/or therapy using brain state information in accordancewith an embodiment of the invention;

FIG. 9 is an illustration of an implantable cardiac device including alead assembly shown implanted in a sectional view of a heart, the deviceused for coordinated patient monitoring, diagnosis, and/or therapy usingbrain state information in accordance with embodiments of the invention;

FIG. 10 is an illustration of a thorax having an implanted subcutaneousmedical device that may be used for coordinated patient monitoring,diagnosis, and/or therapy using brain state information in accordancewith an embodiment of the invention;

FIG. 11 is a block diagram of a cardiac rhythm management (CRM) systemconfigured as a pacemaker and suitable for implementing a sleepdetection methodology in accordance with embodiments of the invention;and

FIG. 12 is a block diagram of a medical system that may be used toimplement coordinated patient monitoring, diagnosis, and/or therapyusing brain state information in accordance with embodiments of theinvention.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings, which form a part hereof, and inwhich are shown by way of illustration, various embodiments by which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the invention.

Detection of brain state may be used to trigger sleep-time therapy in arespiratory and/or cardiac device. A patient's brain state may bedetermined by sensing brain activity of the patient, which may providenormal brain state information such as sleep state/stage, as well asabnormal brain state information such as seizure information. It mayalso be useful to trigger patient monitoring and/or data collection fordiagnostic purposes during sleep. Data acquired during sleep may assistin diagnosing various sleep-related disorders. The collected data may bestored, displayed, printed, or transmitted to a separate device.

Embodiments of the invention include automatic activation, de-activationand/or modification of therapy based on sleep stage. Alternatively, oradditionally, sleep stage information may be used to automaticallyactivate, de-activate and/or modify a number of processes, including forexample, patient monitoring processes and/or diagnostic processes.Therapies may be selectively activated, de-activated, and/or modifiedbased on sleep stage. For example, during deeper sleep stages, lessinvasive therapies such as a pacing therapy may be more desirable than aCPAP therapy. Embodiments may further provide for discrimination betweensleep and wakefulness.

A number of disorders, for example, sleep disordered breathing andmovement disorders such as Periodic Limb Movement Disorder (PLMD), occurprimarily while the patient is asleep. It may be useful to provide afirst therapy while the patient is awake and to trigger a second therapywhile the patient is asleep using brain state information.

Other embodiments of the invention include a device that detects brainstate, such as by using EEG sensor information, and based on thedetected brain state, initiates, de-activates or alters therapy providedby a CRM device and/or a respiratory device. This allows closed loopcontrol of sleep-disordered breathing based on sleep stage, which may bedetermined from the EEG sensor information. The EEG sensor informationmay also be used to detect seizures, and based on seizure detection,control CRM therapy to treat potential arrhythmias.

A significant percentage of patients between the ages of 30 and 60 yearsexperience some symptoms of disordered breathing. Although disorderedbreathing may occur while the patient is awake, it more often occursduring sleep. Sleep disordered breathing is associated with excessivedaytime sleepiness, systemic hypertension, increased risk of stroke,angina and myocardial infarction. Disordered breathing is particularlyprevalent among congestive heart failure patients, and may contribute tothe progression of heart failure.

Various therapies have been used to treat central and/or obstructivedisordered breathing episodes. Obstructive sleep apnea has beenassociated with prolapse of the tongue and its surrounding structureinto the pharynx, thus occluding the respiratory pathway. A commonlyprescribed treatment for obstructive apnea is continuous positive airwaypressure (CPAP). A CPAP device delivers air pressure through a nasalmask worn by the patient. The application of continuous positive airwaypressure keeps the patient's throat open, reducing or eliminating theobstruction causing apnea. The term xPAP will be used herein as ageneric term for any method, system, or device useful for treatment ofapnea, including devices using forms of positive airway pressure,whether continuous pressure or variable pressure, as well as gas therapyand/or oxygen therapy devices.

Cardiac stimulation may alternately or additionally be used as a therapyfor disordered breathing. Therapy methods for disordered breathing basedon cardiac electrical stimulation are described in commonly owned U.S.patent application Ser. No. 10/643,203 (Docket Number GUID.059PA), filedon Aug. 18, 2003, and U.S. patent application Ser. No. 10/643,154(Docket Number GUID.103PA), filed on Aug. 18, 2003 both of which areincorporated by reference herein.

Disorders and diseases affecting the interdependent physiologicalsystems of the human body may be more effectively diagnosed and treatedusing a coordinated approach. Various embodiments of the invention areimplemented using medical systems employing one or a number ofpatient-external and/or patient-internal medical systems. Medicalsystems may communicate or otherwise operate in concert or in astand-alone manner to provide more comprehensive patient monitoring,diagnosis, and therapy.

The following discussion, with reference to FIGS. 1A-1H and 1J,describes embodiments of the invention involving automatic activation,deactivation, modification and/or control of therapy based on sleepstage. Sleep staging may be detected using various approaches,including, for example, by detecting brain activity, skeletal musclemovement, heart rate or other cardiac timing or intervals (e.g., PRinterval), respiratory patterns, and/or other activity/signal that canbe used as a surrogate measurement of sleep. The processes and systemsexemplified by these embodiments may be implemented alone or incombination with one or more processes and systems exemplified by otherembodiments described herein to provide a coordinated approach topatient monitoring, diagnosis, and/or therapy.

Although disordered breathing may occur while the patient is awake, thedisorder is much more prevalent while the patient is sleeping. Invarious embodiments of the invention, sleep stage information is used toenhance sleep disordered breathing therapy and/or diagnosis of a varietyof sleep related disorders.

In accordance with one embodiment, sleep stage detection may be used totrigger therapy for disordered breathing. Using this approach,administration of disordered breathing therapy may be coordinated with aparticular sleep stage. For example, disordered breathing episodes aretypically more frequent during stage 1 or stage 2 sleep. The system mayuse sleep stage detection to deliver the therapy during these sleepstages. REM sleep and sleep stages 3 and 4 are the most restful sleepstages, therefore it is desirable to avoid interruption of sleep duringthese stages. The system may terminate or reduce the level of therapyduring REM sleep and sleep stages 3 and 4 when avoidance of sleepinterruptions are most desirable.

Sleep stage detection may be accomplished using a number of techniques,including, for example, a technique using muscle atonia sensorsdescribed in commonly owned U.S. patent application Ser. No. 10/643,006,filed Aug. 18, 2003, entitled “Sleep State Classification,” which ishereby incorporated herein by reference. Sleep stage detection may alsobe effected using patient-internal or patient-external sensors,including, for example EEG sensors and/or EMG sensors. In oneconfiguration, the sensors, e.g., EEG and/or EMG sensors, used incombination with a respiratory therapy device, such as an xPAP device,may be positioned on the xPAP mask. Sleep stage detection may also bederived from heart rate, cardiac PR intervals (or other cardiac timing),tidal volume, respiratory rate, minute ventilation, body coretemperature, or other physiological measurements that are affected byautonomic control.

Sleep stage information may also be valuable in the context ofdiagnosing various disorders, including sleep-related disorders. Inaccordance with one embodiment, sleep information, including sleeponset, offset, sleep stages, sleep efficiency, sleep latency, and thenumber and degree of arousals may be collected by the system forstorage, display, or transmission to a remote device. The sleep-relatedinformation may be evaluated along with information about detecteddisordered breathing episodes to more fully understand how sleepdisordered breathing affects a particular patient. The use of EEGsensors also allows detection of abnormal brain activity, includingseizures. The EEG sensor information may be collected and used for avariety of diagnostic and therapeutic purposes.

FIG. 1A is a flow chart illustrating a system 50 useful for activating,de-activating or modifying a medical process using brain stateinformation in accordance with embodiments of the invention. The system50 involves sensing brain activity with a sensor 60, either directly,such as by using an EEG sensor to measure brain-waves, or indirectly,such as by using an EMG sensor to measure muscular response toneurostimulation. A brain activity detector 65 receives information fromthe sensor 60 and determines a brain state, which is used by acontroller 70. The controller 70 may control one or both of animplantable medical device 72 and a respiratory therapy unit 74. Theimplantable medical device 72 and/or the respiratory therapy unit 74provides therapy based on information about the sensed brain activity.

A system utilizing sleep stage sensors in connection with the control ofdiagnostic and/or therapeutic functions of a disordered breathing systemin accordance with an embodiment of the invention is illustrated in FIG.1B. In this embodiment, patient-internal or patient-external sensors104, for example EEG and/or EMG sensors, are coupled to a therapy device101. The therapy device 101 includes a sleep stage processor 102 thatanalyzes the sensor signals to detect the patient's sleep state,including sleep offset, onset, and stages of sleep.

The sleep stage processor 102 is coupled to a therapy control unit 103.The therapy control unit 103 may control various types of therapy,including, for example, disordered breathing therapy, cardiac pacingtherapy, respiratory therapy, electrical stimulation therapy, musclestimulation therapy, nerve stimulation therapy, and/or pharmacologicaltherapy, among other therapy types. The therapy control unit 103 usesthe sleep information to initiate, terminate or adjust therapy to thepatient based on the patient's sleep stage.

The therapy device 101 may further include a memory 104 that receivesand stores information from the sleep stage processor 102, the sensors104 and/or other components. The information stored in the memory 105may be displayed and/or downloaded to a remote device, or used for avariety of diagnostic purposes.

Another embodiment of the invention is illustrated in FIG. 1C. Inaccordance with this embodiment, a first therapy device 170 is used tocontrol therapy delivery of a second therapy device 190. The firsttherapy device 170 includes a sleep stage processor 172 coupled tosensors 180, e.g., EEG and/or EMG sensors. The sleep stage processorreceives signals from the sensors 180 and analyzes the sensor signals todetermine sleep onset, offset, and stages of sleep.

Sleep stage information is transferred from the sleep stage processor172 to a first therapy control unit 174 and a second therapy controlunit 176. The therapy control units 174, 176 use the sleep stageinformation to initiate, terminate or modify the therapy delivered bythe first and the second therapy devices 170, 190, respectively, basedon the patient's sleep state.

The first therapy device 170 may also include a memory 177 that receivesand stores information from the sleep stage processor 172, the sensors180 and/or other components. The information stored in the memory 177may be displayed and/or downloaded to a remote device, or used for avariety of diagnostic purposes.

A further embodiment of the invention is illustrated in FIG. 1D.According to this embodiment, first and second therapy devices 110, 130deliver first and second therapies to a patient. The first therapydevice 110 may be implemented as a CRM device, providing cardiac pacingand/or defibrillation therapies to treat various arrhythmias and/or toprovide resynchronization therapy, for example. The CRM device 110 mayalso deliver electrical stimulation therapy to the heart to treatdisordered breathing.

The second therapy device 130 may be implemented as respiratory therapydevice, such as an xPAP device. The xPAP device 130 delivers air orother gas therapy at a controlled pressure to the patient's airway.

EEG sensors 120 are coupled to a sleep stage processor 160 located inthe CRM device 110. Other sensors, such as EMG sensors, may also beincluded. Signals from the EEG and/or other sensors 120 are analyzed bythe sleep stage processor 160 to determine various stages of sleep,including sleep onset, offset, sleep stage, the number and frequency ofarousals, and the degree of arousal.

Information from the sleep stage processor 160 is provided to therespiratory therapy controller 150 located in the CRM device 110. Therespiratory therapy controller 150 uses the sleep stage information toinitiate, terminate, or modify the respiratory therapy based on thesleep stage.

Information from the sleep stage processor 160 and a brain wave analyzer162 is provided to the CRM therapy controller 140. The CRM therapycontroller 140 includes a disordered breathing (DB) therapy control unit142 that uses the sleep stage information to initiate, terminate, ormodify electrical stimulation DB therapy delivered by the CRM device 110based on the patient's sleep state.

The CRM therapy controller 140 may further include an arrhythmia therapycontrol unit 144. Information from the sleep stage processor 160 and thebrain wave analyzer 162 may be used by the arrhythmia therapy controlunit to 144 initiate, terminate, or modify arrhythmia therapy deliveredto the patient.

For example, the CRM therapy controller 140 may decrease the cardiacpacing rate to a sleep rate upon sleep onset and raise the pacing rateat sleep offset. Further, the CRM therapy controller 140 may adjust thepacing therapy delivered to the patient during proarrhythmic sleepperiods, such as REM sleep or the during morning arousal. In oneexample, the arrhythmia therapy control unit 144 may deliver atrialoverdrive pacing during proarrhythmic sleep periods to prevent theoccurrence of arrhythmia.

The EEG sensor signals may also be used by a brain wave analyzer 162 toevaluate brain activity. The brain wave analyzer 162 detects abnormalbrain activity, such as seizures. Patients may have seizures during thenight and not realize that the seizures have occurred. Some seizures areaccompanied by cardiac rhythm disturbances. The brain wave analyzer 162may detect the occurrence of seizures and provide information about theseizures to the arrhythmia therapy control unit 144. The arrhythmiatherapy control unit 144 may modify the CRM therapy to treat cardiacrhythm disturbances cause by, or associated with, seizures. Thearrhythmia therapy control unit 144 may also withhold therapy for rhythmdisturbances that are associated with seizures.

The CRM device 110 may include a memory 164 for storing information fromthe sleep stage processor 160, the brain wave analyzer 162 and othercomponents of the CRM device 110. Stored information may be transferredto a display or other device.

Autonomic arousal responses, as detected using EEG sensors and EMGsensors, are indicative of brain state. Referring now to FIG. 1E, asleep study sensor array output is illustrated including an apnea eventterminating in an arousal. Arousal may be detected from changes in thesympathetic or parasympathetic nervous system. These changes may beeither short-term (i.e., changes associated with individual arousals) orlong-term (i.e., aggregate effect of multiple arousals). A short-termeffect of arousal includes, for example, the activation of sympatheticnerve activities. Sympathetic or parasympathetic changes, or the changesof autonomic balance, may be assessed, for example, by heart ratevariability (HRV), which may be readily detected using a CRM device.

Arousal information may be also used by the sleep stage processor 160 toaugment disordered breathing detection. For example, arousal informationmay be used to confirm occurrences of disordered breathing. Arousalinformation may be used to distinguish between correctly and incorrectlyidentified disordered breathing occurrences indicated by the disorderedbreathing detector. Further, information from arousal detection may beused to separate disordered breathing episodes, e.g., apnea and/orhypopnea, followed by arousal versus those terminated without arousal.The disordered breathing events that are followed by arousal areconsidered to be the most disruptive, as these arousals interrupt thenormal course of sleep and prevent the patient from receiving a fullsleep cycle each night. Detecting these types of disordered breathingevents may enhance the specificity of disordered breathing detection.Further description of the use of arousal information in combinationwith cardiac and xPAP therapies is described in commonly-owned, U.S.patent application identified by Attorney Docket No. GUID.106PA andentitled “Autonomic Arousal Detection System and Method,” filed on Aug.17, 2004 and hereby incorporated herein by reference.

In the graphs of FIG. 1E, the abscissa of all the graphs is the sametime period during the sleep analysis of a patient. The ordinate of eachof the graphs is the signal amplitude of the respective sensor. Traces205, 210, 215, and 220 are the top, second, third, and fourth tracesrespectively, plotted from electrodes adapted to produceelectroencephalograms (EEG). Evident in all four traces, butparticularly pointed out in traces 205 and 210 is an EEG detectedarousal 265. A trace 225 provides an electrocardiogram (EKG) of theheartbeats during the time period of the graph. A trace 230 provides anelectromyogram defining muscular movement during the time period of thegraph. Particularly evident in the trace 230 are arousals indicated byan arousal on EMG 260.

Traces 235, 240, 245, and 250 depict pulmonary activity as sensed bybands placed around the torso. For example, trace 240 is produced usinga band encircling the thorax of the patient, and trace 250 is producedusing a band encircling the abdomen of the patient. Pulmonary activitymay also be sensed through the use of internal sensors, such as, forexample, thoracic impedance sensors and minute ventilation sensors aswill be described further below. Trace 255 depicts the blood oxygensaturation level of the patient.

FIGS. 1F-1H and 1J illustrate various configurations of an EMG sensormechanically coupled to an implanted medical device 320, such as animplantable pacemaker or implantable cardioverter/defibrillator inaccordance with embodiments of the invention, which may be useful forindirectly detecting brain state and activating, de-activating ormodifying medical processes, such as by detecting arousal, sleep-state,seizure, or other indirect detection of brain state and/or brainactivity. The implantable medical device 320 may include a housing 322enclosing the medical device circuitry and a header 324 for coupling alead system 340 to the circuitry of the medical device 320.

An EMG sensor may be implemented, for example, using an electromyogram(EMG) electrode 326 or force responsive sensor 330 positioned on thehousing 322 of the medical device 320 as illustrated in FIGS. 1H and 1J,respectively. FIG. 1H illustrates an EMG sensor 328 positioned on theheader 324 of the medical device 320. Alternatively, an EMG sensor 342,e.g., EMG electrode or strain gauge, may be positioned on the leadsystem 340 or may be coupled to the housing 322 through a catheter orlead system 340, such as by using the header 324, as illustrated in FIG.1J.

FIG. 2 illustrates a method 400 for implantably sensing and detectingbrain state. A brain state sense signal is sensed at a block 402. Brainstate may be sensed, for example, directly using EEG sensors, and/orindirectly using ECG sensors, EEG sensors, EMG sensors, transthoracicimpedance sensors, or other sensors suitable for determining patientbrain state. If the patient is sleeping, brain state may be detectedusing the brain state sense signal illustrated by determination block404.

The brain state detected at determination block 404 provides varioustypes of information recorded at block 406. For example, date, time,sensor data, sense signal amplitudes and/or cycle lengths. This andother information may be useful for updating, developing, and/ordetermining an arousal index, an apnea/hypopnea index, a composite indexand other parameters useful for patient diagnosis and treatment, such asthe automatic activation, de-activation or modification of medicalprocesses. This information may be useful for detecting abnormal brainactivity, such as seizures. The information recorded at block 406 may beuseful, for example, to predict, verify, classify, and/or determine theseverity of a disordered breathing episode and abnormal brain activity.

If intervention and/or treatment is desired at determination block 408,the intervention and/or treatment may be performed at block 410 beforere-starting the method 400. For example, the intervention at block 410may be the automatic activation of a medical process, modification of apatient's CRM stimulation, modification of a disordered breathingtherapy, or other desirable action.

Referring now to FIG. 3, an impedance signal 500 is illustrated.Transthoracic impedance may be useful for detecting sleep-state andother indirect measurements of brain activity, such as seizures, as wellas breathing disorders. The impedance signal 500 may be developed, forexample, from an impedance sense electrode in combination with a CRMdevice. The impedance signal 500 is proportional to the transthoracicimpedance, illustrated as an Impedance 530 on the abscissa of the leftside of the graph in FIG. 3.

The impedance 530 increases during any respiratory inspiration 520 anddecreases during any respiratory expiration 510. The impedance signal500 is also proportional to the amount of air inhaled, denoted by atidal volume 540, illustrated on the abscissa of the right side of thegraph in FIG. 3. The variations in impedance during respiration,identifiable as the peak-to-peak variation of the impedance signal 500,may be used to determine the respiration tidal volume 540. Tidal volume540 corresponds to the volume of air moved in a breath, one cycle ofexpiration 510 and inspiration 520. A minute ventilation may also bedetermined, corresponding to the amount of air moved per a minute oftime 550 illustrated on the ordinate of the graph in FIG. 3.

The onset of breathing disorders may be determined using the impedancesignal 530, and detected breathing disorder information may be used toactivate or modify therapy in accordance with the present invention.During non-REM sleep, a normal respiration pattern includes regular,rhythmic inspiration-expiration cycles without substantialinterruptions. When the tidal volume of the patient's respiration, asindicated by the transthoracic impedance signal, falls below a hypopneathreshold, then a hypopnea event is declared. For example, a hypopneaevent may be declared if the patient's tidal volume falls below about50% of a recent average tidal volume or other baseline tidal volumevalue. If the patient's tidal volume falls further to an apneathreshold, e.g., about 10% of the recent average tidal volume or otherbaseline value, an apnea event is declared.

An adequate quality and quantity of sleep is required to maintainphysiological homeostasis. Prolonged sleep deprivation or periods ofhighly fragmented sleep ultimately has serious health consequences.Chronic lack of sleep may be associated with various cardiac orrespiratory disorders affecting a patient's health and quality of life.Methods and systems for collecting and assessing sleep quality data aredescribed in commonly owned U.S. patent application Ser. No. 10/642,998,entitled “Sleep Quality Data Collection and Evaluation,” filed on Aug.18, 2003, and incorporated herein by reference in its entirety.Evaluation of the patient's sleep patterns and sleep quality may be animportant aspect of providing coordinated therapy to the patient,including respiratory and cardiac therapy.

FIGS. 4-6 are graphs of transthoracic impedance and tidal volume,similar to FIG. 3 previously described. As stated earlier, usingtransthoracic impedance is one indirect method of determining brainstate, such as by detecting sleep state, arousal, and disorderedbreathing, for example. As in FIG. 3, FIGS. 4-6 illustrate the impedancesignal 500 proportional to the transthoracic impedance, againillustrated as Impedance 530 on the abscissa of the left side of thegraphs in FIGS. 4-6. The impedance 530 increases during any respiratoryinspiration 520 and decreases during any respiratory expiration 510. Asbefore, the impedance signal 500 is also proportional to the amount ofair inhaled, denoted the tidal volume 540, illustrated on the abscissaof the right side of the graph in FIGS. 4-6. The magnitude of variationsin impedance and tidal volume during respiration are identifiable as thepeak-to-peak variation of the impedance signal 500.

FIG. 4 illustrates respiration intervals used for disordered breathingdetection useful in accordance with embodiments of the invention.Respiration intervals are used to detect apnea and hypopnea, as well asprovide other sleep-state information for activating, de-activating ormodifying therapy in accordance with the present invention. Detection ofdisordered breathing may involve defining and examining a number ofrespiratory cycle intervals. A respiration cycle is divided into aninspiration period corresponding to the patient inhaling, an expirationperiod, corresponding to the patient exhaling, and a non-breathingperiod occurring between inhaling and exhaling. Respiration intervalsare established using an inspiration threshold 610 and an expirationthreshold 620. The inspiration threshold 610 marks the beginning of aninspiration period 630 and is determined by the transthoracic impedancesignal 500 rising above the inspiration threshold 610. The inspirationperiod 630 ends when the transthoracic impedance signal 500 is a maximum640. The maximum transthoracic impedance signal 640 corresponds to boththe end of the inspiration interval 630 and the beginning of anexpiration interval 650. The expiration interval 650 continues until thetransthoracic impedance 500 falls below an expiration threshold 620. Anon-breathing interval 660 starts from the end of the expiration period650 and continues until the beginning of a next inspiration period 670.

Detection of sleep apnea and severe sleep apnea is illustrated in FIG.5. The patient's respiration signals are monitored and the respirationcycles are defined according to an inspiration 730, an expiration 750,and a non-breathing 760 interval as described in connection with FIG. 4.A condition of sleep apnea is detected when a non-breathing period 760exceeds a first predetermined interval 790, denoted the sleep apneainterval. A condition of severe sleep apnea is detected when thenon-breathing period 760 exceeds a second predetermined interval 795,denoted the severe sleep apnea interval. For example, sleep apnea may bedetected when the non-breathing interval exceeds about 10 seconds, andsevere sleep apnea may be detected when the non-breathing intervalexceeds about 20 seconds.

Hypopnea is a condition of disordered breathing characterized byabnormally shallow breathing. Hypopnea reduces oxygen to the brain, andis linked with altered brain activity and brain states. The alteredbrain activity and brain states indicative of hypopnea may be used toactivate or modify therapy in accordance with the present invention.FIG. 6 is a graph of tidal volume derived from transthoracic impedancemeasurements. The graph of FIG. 6 illustrating the tidal volume of ahypopnea episode may be compared to the tidal volume of a normalbreathing cycle illustrated previously in FIG. 2, which illustratednormal respiration tidal volume and rate. As shown in FIG. 6, hypopneainvolves a period of abnormally shallow respiration, possible at anincreased respiration rate.

Hypopnea is detected by comparing a patient's respiratory tidal volume803 to a hypopnea tidal volume 801. The tidal volume for eachrespiration cycle may be derived from transthoracic impedancemeasurements acquired in the manner described previously. The hypopneatidal volume threshold may be established by, for example, usingclinical results providing a representative tidal volume and duration ofhypopnea events. In one configuration, hypopnea is detected when anaverage of the patient's respiratory tidal volume taken over a selectedtime interval falls below the hypopnea tidal volume threshold.Furthermore, various combinations of hypopnea cycles, breath intervals,and non-breathing intervals may be used to detect hypopnea, where thenon-breathing intervals are determined as described above.

In FIG. 6, a hypopnea episode 805 is identified when the average tidalvolume is significantly below the normal tidal volume. In the exampleillustrated in FIG. 6, the normal tidal volume during the breathingprocess is identified as the peak-to peak value identified as therespiratory tidal volume 803. The hypopnea tidal volume during thehypopnea episode 805 is identified as hypopnea tidal volume 801. Forexample, the hypopnea tidal volume 801 may be about 50% of therespiratory tidal volume 803. The value 50% is used by way of exampleonly, and determination of thresholds for hypopnea events may bedetermined as any value appropriate for a given patient. In the exampleabove, if the tidal volume falls below 50% of the respiratory tidalvolume 803, the breathing episode may be identified as a hypopnea event,originating the measurement of the hypopnea episode 805.

FIG. 7 is a flow chart illustrating a method of apnea and/or hypopneadetection useful for activating, de-activating or modifying therapybased on brain activity in accordance with embodiments of the invention.Various parameters are established 901 before analyzing the patient'srespiration for disordered breathing episodes, including, for example,inspiration and expiration thresholds, sleep apnea interval, severesleep apnea interval, and hypopnea tidal volume (TV) threshold.

The patient's transthoracic impedance is measured 905 as described inmore detail above. If the transthoracic impedance exceeds 910 theinspiration threshold, the beginning of an inspiration interval isdetected 915. If the transthoracic impedance remains below 910 theinspiration threshold, then the impedance signal is checked 905periodically until inspiration 915 occurs.

During the inspiration interval, the patient's transthoracic impedanceis monitored until a maximum value of the transthoracic impedance isdetected 920. Detection of the maximum value signals an end of theinspiration period and a beginning of an expiration period 935.

The expiration interval is characterized by decreasing transthoracicimpedance. When, at determination 940, the transthoracic impedance fallsbelow the expiration threshold, a non-breathing interval is detected955.

If the transthoracic impedance determination 960 does not exceed theinspiration threshold within a first predetermined interval, denoted thesleep apnea interval 965, then a condition of sleep apnea is detected970. Severe sleep apnea 980 is detected if the non-breathing periodextends beyond a second predetermined interval, denoted the severe sleepapnea interval 975.

When the transthoracic impedance determination 960 exceeds theinspiration threshold, the tidal volume from the peak-to-peaktransthoracic impedance is calculated, along with a moving average ofpast tidal volumes 985. The peak-to-peak transthoracic impedanceprovides a value proportional to the tidal volume of the respirationcycle. This value is compared at determination 990 to a hypopnea tidalvolume threshold. If, at determination 990, the peak-to-peaktransthoracic impedance is consistent with the hypopnea tidal volumethreshold for a predetermined time 992, then a hypopnea cycle 995 isdetected.

According to one embodiment of the invention, illustrated in FIG. 8, amedical system 1000 may include an implantable cardiac rhythm managementdevice 1010 that cooperates with a patient-external respiration therapydevice 1020 to provide coordinated patient monitoring, diagnosis and/ortherapy. In the example illustrated in FIG. 8, a mechanical respirationtherapy device, designated CPAP device 1020, includes a positive airwaypressure device that cooperates with a CRM 1010. Positive airwaypressure devices may be used to provide a variety of respirationtherapies, including, for example, continuous positive airway pressure(CPAP), bi-level positive airway pressure (bi-level PAP), proportionalpositive airway pressure (PPAP), auto-titrating positive airwaypressure, ventilation, gas or oxygen therapies. Such devices may also beconfigured to provide negative airway pressure on a selective basis asneeded, such as in the treatment of Cheyne-Stokes breathing. Thesetherapies may be activated, de-activated or adjusted based on brainstate in accordance with the present invention.

The CPAP device 1020 develops a positive air pressure that is deliveredto the patient's airway through a tube system 1052 and a mask 1054connected to the CPAP device 1020. The mask 1054 may include EEGsensors, such as an EEG sensor 1056 attached to a strap 1057 that isplaced around a head 1055 of the patient. Positive airway pressuredevices are often used to treat disordered breathing. In oneconfiguration, for example, the positive airway pressure provided by theCPAP device 1020 acts as a pneumatic splint keeping the patient's airwayopen and reducing the severity and/or number of occurrences ofdisordered breathing due to airway obstruction.

The CPAP device 1020 may directly control the delivery of respirationtherapy to the patient, and may contribute to the control of the CRMdevice 1010. In addition, the CPAP device 1020 may provide a number ofmonitoring and/or diagnostic functions in relation to the respiratorysystem and/or other physiological systems.

The CRM 1010 and CPAP 1020 devices may communicate directly through awireless communications link 1017, for example. Alternatively, oradditionally, the CRM 1010 and CPAP 1020 devices may communicate withand/or through an APM such as an APM system 1030, as will be describedfurther below with reference to FIG. 12. The CRM 1010 may be coupled toa heart 1040 of the patient using a lead system 1015, for example.

The CRM 1010 may provide a first set of monitoring, diagnostic, and/ortherapeutic functions to a patient 1055. The CRM 1010 may beelectrically coupled to a patient's heart 1040 through one or morecardiac electrodes 1015 terminating in, on, or about the heart 1040. Thecardiac electrodes 1015 may sense cardiac signals produced by the heart1040 and/or provide therapy to one or more heart chambers. For example,the cardiac electrodes 1015 may deliver electrical stimulation to one ormore heart 1040 chambers, and/or to one or multiple sites within theheart 1040 chambers. The CRM 1010 may directly control delivery of oneor more cardiac therapies, such as cardiac pacing, defibrillation,cardioversion, cardiac resynchronization, and/or other cardiactherapies, for example. In addition, the CRM 1010 may facilitate thecontrol of a mechanical respiration device 1020. Further, the CRM 1010may perform various monitoring and/or diagnostic functions in relationto the cardiovascular system and/or other physiological systems.

Although FIG. 8 illustrates a CRM device 1010 used with a CPAP device1020 to provide coordinated patient monitoring, diagnosis and/ortherapy, any number of patient-internal and patient-external medicaldevices may be included in a medical system in accordance with theinvention. For example, a drug delivery device, such as a drug pump orcontrollable nebulizer, may be included in the system 1000. The drugdelivery device may cooperate with either or both of the CRM device 1010and the CPAP device 1020 and may contribute to the patient monitoring,diagnosis, and/or therapeutic functions of the medical system 1000.

FIG. 9 is a partial view of an implantable CRM device that may includecircuitry 1104 to activate, deactivate, or modify therapies based onbrain state in accordance with embodiments of the invention. In thisexample, the implantable CRM device comprises an implantable pulsegenerator 1100 electrically and physically coupled to an intracardiaclead system 1102. Portions of the intracardiac lead system 1102 areinserted into the patient's heart 1101. The intracardiac lead system1102 includes one or more electrodes configured to sense electricalcardiac activity of the heart, deliver electrical stimulation to theheart, sense the patient's transthoracic impedance, and/or sense otherphysiological parameters, e,g, cardiac chamber pressure or temperature.Portions of the housing 1191 of the pulse generator 1100 may optionallyserve as a can electrode.

Communications circuitry is disposed within the housing 1191 forfacilitating communication between the pulse generator 1100 and anexternal communication device, such as a portable or bed-sidecommunication station, patient-carried/worn communication station, orexternal programmer, for example. The communications circuitry can alsofacilitate unidirectional or bidirectional communication with one ormore implanted, external, cutaneous, or subcutaneous physiologic ornon-physiologic sensors, patient-input devices and/or informationsystems.

The pulse generator 1100 may optionally incorporate movement sensor 1192that may be used o implement rate adaptive pacing. The movement sensor1192 may be implemented as an accelerometer positioned in or on thehousing 1191 of the pulse generator 1100. If the movement sensor 1192 isimplemented as an accelerometer, the movement sensor 1192 may alsoprovide respiratory, e.g. snoring, rales, coughing, and cardiac, e.g.S1-S4 heart sounds, murmurs, and other acoustic information.

The lead system 1102 of the CRM device may incorporate one or moretransthoracic impedance sensors that may be used to acquire thepatient's respiration waveform, or other respiration-relatedinformation. The transthoracic impedance sensor may include, forexample, one or more intracardiac electrodes 1116, 1114, 1154, 1156,1112, 1117, 1113, 1161 positioned in one or more chambers of the heart590. The intracardiac electrodes 1116, 1114, 1154, 1156, 1112, 1117,1113, 1161 may be coupled to impedance drive/sense circuitry 1106positioned within the housing 1191 of the pulse generator 1100.

In one implementation, impedance drive/sense circuitry 1106 generates acurrent that flows through the tissue between an impedance driveelectrode 1154 and a can electrode on the housing 1191 of the pulsegenerator 1100. The voltage at an impedance sense electrode 1156relative to the can electrode changes as the patient's transthoracicimpedance changes. The voltage signal developed between the impedancesense electrode 1156 and the can electrode is detected by the impedancesense circuitry 1106. Other locations and/or combinations of impedancesense and drive electrodes are also possible.

The voltage signal developed at the impedance sense electrode 1156 isproportional to the patient's transthoracic impedance and represents thepatient's respiration waveform. The transthoracic impedance increasesduring respiratory inspiration and decreases during respiratoryexpiration. The peak-to-peak transition of the transthoracic impedanceis proportional to the amount of air moved in one breath, denoted thetidal volume. The amount of air moved per minute is denoted the minuteventilation. A normal “at rest” respiration pattern, e.g., duringnon-REM sleep, includes regular, rhythmic inspiration-expiration cycleswithout substantial interruptions.

The lead system 1102 may include one or more cardiac pace/senseelectrodes 1154, 1156, 1112, 1117, 1113 positioned in, on, or about oneor more heart chambers for sensing electrical signals from the patient'sheart 1101 and/or delivering pacing pulses to the heart 1101. Theintracardiac sense/pace electrodes 1154, 1156, 1112, 1117, 1113, such asthose illustrated in FIG. 9, may be used to sense and/or pace one ormore chambers of the heart, including the left ventricle, the rightventricle, the left atrium and/or the right atrium. The lead system 1102may include one or more defibrillation electrodes 1116, 1114 fordelivering defibrillation/cardioversion shocks to the heart.

The pulse generator 1100 may include circuitry for detecting cardiacarrhythmias and/or for controlling pacing or defibrillation therapy inthe form of electrical stimulation pulses or shocks delivered to theheart through the lead system 1102. Circuitry 1104 for activating,deactivating, and/or modifying therapy based on brain state may behoused within the pulse generator 1100. The brain state activationcircuitry 1104 may be coupled to various sensors, patient input devices,and/or other information systems through leads or through wirelesscommunication links as described herein.

FIG. 10 is a diagram illustrating a subcutaneous implantable medicaldevice 1200 that may be used for detecting brain state and activating,deactivating or modifying medical processes in accordance withembodiments of the invention. The device 1200 illustrated in FIG. 10 isan ITCS device that may be implanted under the skin in the chest regionof a patient. The ITCS device may, for example, be implantedsubcutaneously such that all or selected elements of the device arepositioned on the patient's front, back, side, or other body locationssuitable for sensing cardiac activity and delivering cardiac stimulationtherapy. It is understood that elements of the ITCS device may belocated at several different body locations, such as in the chest,abdominal, or subclavian region with electrode elements respectivelypositioned at different regions near, around, in, or on the heart.

The primary housing (e.g., the active or non-active can) of the ITCSdevice, for example, may be configured for positioning outside of a ribcage 1250 at an intercostal or subcostal location, within the abdomen,or in the upper chest region (e.g., subclavian location, such as above athird rib 1253). In one implementation, one or more electrodes may belocated on a primary housing 1272 and/or at other locations about, butnot in direct contact with the heart, great vessel or coronaryvasculature.

In another implementation, one or more electrodes may be located indirect contact with the heart, great vessel or coronary vasculature,such as via one or more leads implanted by use of conventionaltransvenous delivery approaches. In another implementation, for example,one or more subcutaneous electrode subsystems or electrode arrays may beused.to sense cardiac activity and deliver cardiac stimulation energy inan ITCS device configuration employing an active can or a configurationemploying a non-active can. Electrodes may be situated at anteriorand/or posterior locations relative to the heart.

In particular configurations, systems and methods may perform functionstraditionally performed by pacemakers, such as providing various pacingtherapies as are known in the art, in addition tocardioversion/defibrillation therapies. Exemplary pacemaker circuitry,structures and functionality, aspects of which may be incorporated in anITCS device of a type that may benefit from multi-parameter sensingconfigurations, are disclosed in commonly owned U.S. Pat. No. 4,562,841;5,284,136; 5,376,476; 5,036,849; 5,540,727; 5,836,987; 6,044,298; and6,055,454, which are hereby incorporated herein by reference in theirrespective entireties. It is understood that ITCS device configurationsmay provide for non-physiologic pacing support in addition to, or to theexclusion of, bradycardia and/or anti-tachycardia pacing therapies.

An ITCS device in accordance with various embodiments may implementdiagnostic and/or monitoring functions as well as provide cardiacstimulation therapy. Diagnostics functions may involve storing,trending, displaying, transmitting, and/or evaluating variousindications based on the detection of EMG. Exemplary cardiac monitoringcircuitry, structures and functionality, aspects of which may beincorporated in an ITCS of the invention, are disclosed in commonlyowned U.S. Pat. No. 5,313,953; 5,388,578; and 5,411,031, which arehereby incorporated herein by reference in their respective entireties.

An ITCS device may be used to implement various diagnostic functions,which may involve performing rate-based, pattern and rate-based, and/ormorphological tachyarrhythmia discrimination analyses. Subcutaneous,cutaneous, and/or external sensors, such as those previously described,may be employed to acquire physiologic and non-physiologic informationfor purposes of enhancing tachyarrhythmia detection and termination. Itis understood that configurations, features, and combination of featuresdescribed in the present disclosure may be implemented in a wide rangeof implantable medical devices, and that such embodiments and featuresare not limited to the particular devices described herein.

In FIG. 10, there is shown a configuration of a transthoracic cardiacsensing and/or stimulation (ITCS) device having components implanted inthe chest region of a patient at different locations. In the particularconfiguration shown in FIG. 10, the ITCS device includes the housing1272 within which various cardiac sensing, detection, processing, andenergy delivery circuitry may be housed. It is understood that thecomponents and functionality depicted in the figures and describedherein may be implemented in hardware, software, or a combination ofhardware and software. It is further understood that the components andfunctionality depicted as separate or discrete blocks/elements in thefigures in general may be implemented in combination with othercomponents and functionality, and that the depiction of such componentsand functionality in individual or integral form is for purposes ofclarity of explanation, and not of limitation.

Communications circuitry may be disposed within the housing 1272 forfacilitating communication between the ITCS device and an externalcommunication device, such as a portable or bedside communicationstation, patient-carried/worn communication station, or externalprogrammer, for example. The communications circuitry may alsofacilitate unidirectional or bidirectional communication with one ormore external, cutaneous, or subcutaneous physiologic or non-physiologicsensors. The housing 1272 is typically configured to include one or moreelectrodes (e.g., can electrode and/or indifferent electrode). Althoughthe housing 1272 is typically configured as an active can, it isappreciated that a non-active can configuration may be implemented, inwhich case at least two electrodes spaced apart from the housing 1272are employed.

In the configuration shown in FIG. 10, a subcutaneous electrode 1274 maybe positioned under the skin in the chest region and situated distalfrom the housing 1272. The subcutaneous and, if applicable, housingelectrode(s) may be positioned about the heart at various locations andorientations, such as at various anterior and/or posterior locationsrelative to the heart. The subcutaneous electrode 1274 is coupled tocircuitry within the housing 1272 via a lead assembly 1276. One or moreconductors (e.g., coils or cables) are provided within the lead assembly1276 and electrically couple the subcutaneous electrode 1274 withcircuitry in the housing 1272. One or more sense, sense/pace ordefibrillation electrodes may be situated on the elongated structure ofthe electrode support, the housing 1272, and/or the distal electrodeassembly (shown as subcutaneous electrode 1274 in the configurationshown in FIG. 10).

In one configuration, the electrode support assembly and the housing1272 define a unitary structure (e.g., a single housing/unit). Theelectronic components and electrode conductors/connectors are disposedwithin or on the unitary ITCS device housing/electrode support assembly.At least two electrodes are supported on the unitary structure nearopposing ends of the housing/electrode support assembly. The unitarystructure may have an arcuate or angled shape, for example.

According to another configuration, the electrode support assemblydefines a physically separable unit relative to the housing 1272. Theelectrode support assembly includes mechanical and electrical couplingsthat facilitate mating engagement with corresponding mechanical andelectrical couplings of the housing 1272. For example, a header blockarrangement may be configured to include both electrical and mechanicalcouplings that provide for mechanical and electrical connections betweenthe electrode support assembly and housing 1272. The header blockarrangement may be provided on the housing 1272 or the electrode supportassembly. Alternatively, a mechanical/electrical coupler may be used toestablish mechanical and electrical connections between the electrodesupport assembly and housing 1272. In such a configuration, a variety ofdifferent electrode support assemblies of varying shapes, sizes, andelectrode configurations may be made available for physically andelectrically connecting to a standard ITCS device housing 1272.

Various embodiments described herein may be used in connection withsubcutaneous monitoring, diagnosis, and/or therapy. Methods, structures,and/or techniques described herein relating to subcutaneous systems andmethods may incorporate features of one or more of the followingreferences: commonly owned US Patent Applications: “Subcutaneous CardiacSensing, Stimulation, Lead Delivery, and Electrode Fixation Systems andMethods,” Ser. No. 60/462,272, filed Apr. 11, 2003; “ReconfigurableSubcutaneous Cardiac Device,” Ser. No: 10/821,248, filed: Apr. 8, 2004;and “Subcutaneous Cardiac Rhythm Management,” Ser. No: 10/820,642,filed: Apr. 8, 2004; each hereby incorporated herein by reference.

Referring now to FIG. 11, there is shown a block diagram of anembodiment of a CRM system 1300 configured as a pacemaker and suitablefor implantably detecting brain state and activating, de-activating ormodifying medical processes in accordance with the invention. FIG. 11shows the CRM 1300 divided into functional blocks. The CRM 1300 includesa sleep detector 1320 for receiving sleep-related signals and detectingsleep in accordance with embodiments of the invention.

In one embodiment, the sleep detector 1320 is incorporated as part ofCRM circuitry 1310 encased and hermetically sealed in a housing 1301suitable for implanting in a human body. Power to the CRM 1300 issupplied by an electrochemical battery power supply 1312 housed withinthe CRM 1300. A connector block (not shown) is additionally attached tothe CRM 1300 to allow for the physical and electrical attachment of thecardiac lead system conductors to the CRM circuitry 1310.

The CRM circuitry 1310 may be configured as a programmablemicroprocessor-based system, with circuitry for detecting sleep inaddition to providing pacing therapy to the heart. Cardiac signalssensed by one or more cardiac electrodes 1341 may be processed by thecardiac event detection circuitry 1360. Pace pulses controlled by thepacemaker control 1350 and generated by the pulse generator 1340 aredelivered to the heart to treat various arrhythmias of the heart.

The memory circuit 1316 may store parameters for various deviceoperations involved in sleep detection and/or cardiac pacing andsensing. The memory circuit 1316 may also store data indicative ofsleep-related signals received by components of the CRM circuitry 1310,such as information derived from one or more impedance electrodes 1395,the cardiac signal detector system 1360, the accelerometer 1335, and/orthe sleep detector 1320.

As illustrated in FIG. 11, the sleep detector 1320 receives signalsderived from the cardiac event detector 1360, the impedance electrodes1395 and the accelerometer 1335 to perform operations involvingdetecting sleep onset and sleep termination according to the principlesof the invention. Historical data storage 1318 may be coupled to thesleep detection circuitry 1320 for storing historical sleep relateddata. Such data may be transmitted to an external programmer unit 1380and used for various diagnostic purposes and as needed or desired.

Telemetry circuitry 1314 is coupled to the CRM circuitry 1310 to allowthe CRM 1300 to communicate with a remote device such as the programmer1380, or other device such as a patient-external EEG sensor. In oneembodiment, the telemetry circuitry. 1314 and the programmer 1380 use awire loop antenna and a radio frequency telemetric link to receive andtransmit signals and data between the programmer 1380 and telemetrycircuitry 1314. In this manner, programming commands and data (such asEEG data) may be transferred between the CRM circuitry 1310 and the oneor more remote devices 1380 during and after implant.

The programming commands allow a physician to set or modify variousparameters used by the CRM system 1300. These parameters may includesetting sleep detection parameters for use during sleep detection, suchas which sleep-related signals are to be used for sleep detection andthreshold adjustment, and the initial sleep detection thresholds. Inaddition, the CRM system 1300 may download to the programmer 1380 storeddata pertaining to sensed sleep periods, including the amount of timespent sleeping, the time of day sleep periods occurred, historical dataof sleep times, and the number of arousals during the sleep periods, forexample.

Still referring to FIG. 11, signals associated with patient activity,indicative of brain state, may be detected through the use of anaccelerometer 1335 positioned within the housing 1301 of the CRM 1300.The accelerometer 1335 may be responsive to patient activity. Theaccelerometer signal may be correlated with activity level or workload,for example. Signals derived from the accelerometer 1335 are coupled tothe sleep detector 1320 and may also be used by the pacemaker 1350 forimplementing a rate adaptive pacing regimen, for example.

The impedance electrodes 1395 sense the patient's transthoracicimpedance. As described earlier, transthoracic impedance may also beuseful as an indirect measure of brain state. The transthoracicimpedance may be used to calculate various parameters associated withrespiration. Impedance driver circuitry (not shown) induces a currentthat flows through the blood between the impedance drive electrode and acan electrode on the housing 1301 of the CRM 1300. The voltage at animpedance sense electrode relative to the can electrode changes as thetransthoracic impedance changes. The voltage signal developed betweenthe impedance sense electrode and the can electrode is detected by theimpedance sense amplifier and is delivered to the sleep detectorcircuitry 1320 for further processing.

FIG. 12 is a block diagram of a medical system 1400 that may be used toimplement coordinated patient measuring and/or monitoring, diagnosis,and/or therapy, including detecting EEG's and determining the brainstate in accordance with embodiments of the invention. The medicalsystem 1400 may include, for example, one or more patient-internalmedical devices 1410 and one or more patient-external medical devices1420. Each of the patient-internal 1410 and patient-external 1420medical devices may include one or more of a patient monitoring unit1412, 1422, a diagnostics unit 1414, 1424, and/or a therapy unit 1416,1426.

The patient-internal medical device 1410 is typically a fully orpartially implantable device that performs measuring, monitoring,diagnosis, and/or therapy functions. The patient-external medical device1420 performs monitoring, diagnosis and/or therapy functions external tothe patient (i.e., not invasively implanted within the patient's body).The patient-external medical device 1420 may be positioned on thepatient, near the patient, or in any location external to the patient.It is understood that a portion of a patient-external medical device1420 may be positioned within an orifice of the body, such as the nasalcavity or mouth, yet may be considered external to the patient (e.g.,mouth pieces/appliances, tubes/appliances for nostrils, or temperaturesensors positioned in the ear canal).

The patient-internal and patient-external medical devices 1410,1420 maybe coupled to one or more sensors 1441, 1442, 1445, 1446, patient inputdevices 1443, 1447 and/or other information acquisition devices 1444,1448. The sensors 1441, 1442, 1445, 1446, patient input devices 1443,1447, and/or other information acquisition devices 1444, 1448 may beemployed to detect conditions relevant to the monitoring, diagnostic,and/or therapeutic functions of the patient-internal andpatient-external medical devices 1410, 1420.

The medical devices 1410, 1420 may each be coupled to one or morepatient-internal sensors 1441, 1445 that are fully or partiallyimplantable within the patient. The medical devices 1410, 1420 may alsobe coupled to patient-external sensors positioned on, near, or in aremote location with respect to the patient. For example, thepatient-external sensors 1442 may include EEG sensors useful fordetecting brain activity. The patient-internal and patient-externalsensors may also be used to sense conditions, such as physiological orenvironmental conditions, that affect the patient.

The patient-internal sensors 1441 may be coupled to the patient-internalmedical device 1410 through one or more internal leads 1453. In oneexample, as was described above with reference to FIG. 9, an internalendocardial lead system is used to couple cardiac electrodes to animplantable pacemaker or other cardiac rhythm management device. Stillreferring to FIG. 12, one or more patient-internal sensors 1441 may beequipped with transceiver circuitry to support wireless communicationsbetween the one or more patient-internal sensors 1441 and thepatient-internal medical device 1410 and/or the patient-external medicaldevice 1420.

The patient-external sensors 1442 may be coupled to the patient-internalmedical device 1410 and/or the patient-external medical device 1420through one or more internal leads 1455 or through wireless connections.Patient-external sensors 1442 may communicate with the patient-internalmedical device 1410 wirelessly. Patient-external sensors 1446 may becoupled to the patient-external medical device 1420 through one or moreinternal leads 1457 or through a wireless link.

The medical devices 1410, 1420 may be coupled to one or more patientinput devices 1443, 1447. The patient input devices are used to allowthe patient to manually transfer information to the medical devices1410, 1420. The patient input devices 1443, 1447 may be particularlyuseful for inputting information concerning patient perceptions, such ashow well the patient feels, and information such as patient smoking,drug use, or other activities that are not automatically sensed ordetected by the medical devices 1410, 1420.

The medical devices 1410, 1420 may be connected to one or moreinformation acquisition devices 1444, 1448, for example, a database thatstores information useful in connection with the monitoring, diagnostic,or therapy functions of the medical devices 1410, 1420. For example, oneor more of the medical devices 1410, 1420 may be coupled through anetwork to a patient information server 1430 that provides informationabout environmental conditions affecting the patient, e.g., thepollution index for the patient's location.

In one embodiment, the patient-internal medical device 1410 and thepatient-external medical device 1420 may communicate through a wirelesslink between the medical devices 1410, 1420. For example, thepatient-internal and patient-external devices 1410, 1420 may be coupledthrough a short-range radio link, such as Bluetooth, IEEE 802.11, and/ora proprietary wireless protocol. The communications link may facilitateunidirectional or bidirectional communication between thepatient-internal 1410 and patient-external 1420 medical devices. Dataand/or control signals may be transmitted between the patient-internal1410 and patient-external 1420 medical devices to coordinate thefunctions of the medical devices 1410, 1420.

In another embodiment, the patient-internal and patient-external medicaldevices 1410,1420 may be used within the structure of an advancedpatient management system 1440. Advanced patient management systems 1440involve a system of medical devices that are accessible through variouscommunications technologies. For example, patient data may be downloadedfrom one or more of the medical devices periodically or on command, andstored at the patient information server 1430. The physician and/or thepatient may communicate with the medical devices and the patientinformation server 1430, for example, to acquire patient data or toinitiate, terminate or modify therapy.

The data stored on the patient information server 1430 may be accessibleby the patient and the patient's physician through one or more terminals1450, e.g., remote computers located in the patient's home or thephysician's office. The patient information server 1430 may be used tocommunicate to one or more of the patient-internal and patient-externalmedical devices 1410, 1420 to provide remote control of the monitoring,diagnosis, and/or therapy functions of the medical devices 1410, 1420.

In one embodiment, the patient's physician may access patient datatransmitted from the medical devices 1410, 1420 to the patientinformation server 1430. After evaluation of the patient data, thepatient's physician may communicate with one or more of thepatient-internal or patient-external devices 1410, 1420 through the APMsystem 1440 to initiate, terminate, or modify the monitoring,diagnostic, and/or therapy functions of the patient-internal and/orpatient-external medical systems 1410, 1420. Systems and methodsinvolving advanced patient management techniques are further describedin U.S. Pat. Nos. 6,336,903, 6,312,378, 6,270,457, and 6,398,728, herebyincorporated herein by reference.

In another embodiment, the patient-internal and patient-external medicaldevices 1410, 1420 may not communicate directly, but may communicateindirectly through the APM system 1440. In this embodiment, the APMsystem 1440 may operate as an intermediary between two or more of themedical devices 1410, 1420. For example, data and/or control informationmay be transferred from one of the medical devices 1410, 1420 to the APMsystem 1440. The APM system 1440 may transfer the data and/or controlinformation to another of the medical devices 1410, 1420.

In one embodiment, the APM system 1440 may communicate directly with thepatient-internal and/or patient-external medical devices 1410, 1420. Inanother embodiment, the APM system 1440 may communicate with thepatient-internal and/or patient-external medical devices 1410, 1420through medical device programmers 1460, 1470 respectively associatedwith each medical device 1410, 1420.

Various embodiments described herein may be used in connection withadvanced patient management. Methods, structures, and/or techniquesdescribed herein relating to advanced patient management, such as thoseinvolving remote patient/device monitoring, diagnosis, therapy, or otheradvanced patient management related methodologies, may incorporatefeatures of one or more of the following references: U.S. Pat. Nos.6,221,011; 6,277,072; 6,280,380; 6,358,203; 6,368,284; and 6,440,066each hereby incorporated herein by reference.

A number of the examples presented herein involve block diagramsillustrating functional blocks used for coordinated monitoring,diagnosis and/or therapy functions in accordance with embodiments of theinvention. It will be understood by those skilled in the art that thereexist many possible configurations in which these functional blocks maybe arranged and implemented. The examples depicted herein provideexamples of possible functional arrangements used to implement theapproaches of the invention.

Each feature disclosed in this specification (including any accompanyingclaims, abstract, and drawings), may be replaced by alternative featureshaving the same, equivalent or similar purpose, unless expressly statedotherwise. Thus, unless expressly stated otherwise, each featuredisclosed is one example only of a generic series of equivalent orsimilar features.

Various modifications and additions can be made to the embodimentsdiscussed hereinabove without departing from the scope of the presentinvention. Accordingly, the scope of the present invention should not belimited by the particular embodiments described above, but should bedefined only by the claims set forth below and equivalents thereof.

1. A system, comprising: a sensor system having one or more sensorsconfigured to sense brain activity; a brain activity detector coupled tothe sensor system and configured to determine a brain state based onsignals received from the sensor system; a medical system configured toperform at least one respiratory or cardiac process; and a controllercoupled to the brain activity detector and the medical system, thecontroller configured to activate, de-activate or adjust the at leastone cardiac or respiratory process based on the brain state.
 2. Thesystem of claim 1, wherein the sensor system comprises at least one EEGsensor.
 3. The system of claim 1, wherein the sensor system comprises atleast one EEG sensor and at least one EMG sensor.
 4. The system of claim1, wherein the sensor system comprises at least one respiratory sensor.5. The system of claim 1, wherein the brain activity detector isconfigured to detect sleep stage.
 6. The system of claim 1, wherein themedical system comprises an external respiratory therapy device.
 7. Thesystem of claim 6, wherein the controller is disposed in the externalrespiratory therapy device.
 8. The system of claim 1, wherein themedical system comprises an implantable cardiac rhythm managementdevice.
 9. The system of claim 8, wherein the controller is disposed inthe implantable cardiac rhythm management device.
 10. The system ofclaim 1, wherein the medical system comprises a cardiac rhythmmanagement device and an external respiratory therapy device.
 11. Thesystem of claim 1, wherein the system comprises a communicationsinterface configured for effecting communications with a network serversystem, and the controller comprises a controller of the network serversystem.
 12. The system of claim 1, further comprising a display coupledto controller.
 13. A method, comprising: sensing signals indicative ofbrain activity; determining a brain state of a patient based on thesensed signals; and controlling at least one of a respiratory or acardiac medical process based on brain state.
 14. The method of claim13, wherein sensing the signals indicative of brain state comprisessensing respiration signals.
 15. The method of claim 13, wherein:sensing signals related to brain state comprises determining a sleepstage of the patient; and controlling the at least one medical processcomprises activating, de-activating or adjusting therapy based on thepatient's sleep stage.
 16. The method of claim 13, wherein: sensingsignals related to brain state comprises sensing the signals indicativeof seizure; and controlling the at least one medical process comprisesactivating, de-activating or adjusting arrhythmia therapy based on thesignals indicative of seizure.
 17. The method of claim 13, whereinsensing signals comprises sensing at least one EEG signal and at leastone EMG signal.
 18. The method of claim 13, wherein controlling the atleast one medical process comprises activating, de-activating oradjusting a respiratory therapy.
 19. The method of claim 13, whereincontrolling the at least one medical process comprises activating,de-activating or adjusting a cardiac pacing therapy.
 20. A medicalsystem, comprising: means for sensing signals related to brain activity;means for determining a brain state of a patient based on the sensedsignals; and means for activating, de-activating or modifying at leastone of a respiratory or cardiac medical process based on brain state.